Talmapimod

Identification

Name
Talmapimod
Accession Number
DB05412
Type
Small Molecule
Groups
Investigational
Description

Talmapimod is the first-generation oral p38 MAP kinase inhibitor developed by Scios. It has shown to be effective to cure inflammatory diseases such as Rheumatoid Arthritis.

Structure
Thumb
Synonyms
Not Available
External IDs
SCIO-469
Categories
Not Available
UNII
B1E00KQ6NT
CAS number
309913-83-5
Weight
Average: 513.004
Monoisotopic: 512.199046758
Chemical Formula
C27H30ClFN4O3
InChI Key
ZMELOYOKMZBMRB-DLBZAZTESA-N
InChI
InChI=1S/C27H30ClFN4O3/c1-16-13-33(17(2)12-32(16)14-18-6-8-19(29)9-7-18)26(35)21-10-20-22(25(34)27(36)30(3)4)15-31(5)24(20)11-23(21)28/h6-11,15-17H,12-14H2,1-5H3/t16-,17+/m0/s1
IUPAC Name
2-{6-chloro-5-[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine-1-carbonyl]-1-methyl-1H-indol-3-yl}-N,N-dimethyl-2-oxoacetamide
SMILES
[H][[email protected]]1(C)CN(C(=O)C2=C(Cl)C=C3N(C)C=C(C(=O)C(=O)N(C)C)C3=C2)[[email protected]]([H])(C)CN1CC1=CC=C(F)C=C1

Pharmacology

Indication

Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

SCIO-469 inhibits p38 kinase, a stimulatory modulator of pro-inflammatory factors including tumor necrosis factor-alpha (TNFa), interleukin-1 (IL-1), and cyclooxygenase-2 (COX-2), all of which are known to contribute to both symptoms and disease progression in patients with Rheumatoid Arthritis (RA). Existing protein-based products that antagonize TNFa have been shown to markedly relieve the symptoms and retard the progression of RA. It also has the potential for additional benefits associated with its inhibition of IL-1 and COX-2.

TargetActionsOrganism
UMitogen-activated protein kinase 14Not AvailableHuman
UTumor necrosis factorNot AvailableHuman
UInterleukin-1 betaNot AvailableHuman
UCytochrome c oxidase subunit 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Vanderkerken K, Medicherla S, Coulton L, De Raeve H, Willems A, Lawson M, Van Camp B, Protter AA, Higgins LS, Menu E, Croucher PI: Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma. Cancer Res. 2007 May 15;67(10):4572-7. Epub 2007 May 10. [PubMed:17495322]
  2. Nguyen AN, Stebbins EG, Henson M, O'Young G, Choi SJ, Quon D, Damm D, Reddy M, Ma JY, Haghnazari E, Kapoun AM, Medicherla S, Protter A, Schreiner GF, Kurihara N, Anderson J, Roodman GD, Navas TA, Higgins LS: Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation. Exp Cell Res. 2006 Jun 10;312(10):1909-23. Epub 2006 Apr 4. [PubMed:16600214]
External Links
PubChem Compound
9871074
PubChem Substance
347827727
ChemSpider
8046764
BindingDB
50266947
ChEBI
90683
ChEMBL
CHEMBL514201
HET
469
PDB Entries
3hub / 3zsh

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentBone Marrow Diseases / Bone Marrow Neoplasms / Hematologic Diseases / Myelodysplastic Syndromes1
2CompletedTreatmentMultiple Myeloma (MM)2
2CompletedTreatmentRheumatoid Arthritis2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00586 mg/mLALOGPS
logP3.78ALOGPS
logP3.9ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)5.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area65.86 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity139.25 m3·mol-1ChemAxon
Polarizability54.44 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolecarboxamides and derivatives. These are compounds containing a carboxamide group attached to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxamides and derivatives
Alternative Parents
N-alkylindoles / Indoles / Benzylamines / Aryl ketones / Phenylmethylamines / Aralkylamines / N-alkylpiperazines / Fluorobenzenes / Aryl chlorides / Aryl fluorides
show 13 more
Substituents
Indolecarboxamide derivative / N-alkylindole / Indole / Phenylmethylamine / Aryl ketone / Benzylamine / Fluorobenzene / Aralkylamine / Halobenzene / N-alkylpiperazine
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Cytochrome-c oxidase activity
Specific Function
Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Subunit 2 transfers the ...
Gene Name
MT-CO2
Uniprot ID
P00403
Uniprot Name
Cytochrome c oxidase subunit 2
Molecular Weight
25564.73 Da

Drug created on November 18, 2007 11:24 / Updated on December 01, 2017 15:36